Ordering Recommendation

Diagnostic and predictive testing for juvenile polyposis syndrome (JPS) or JPS/hereditary hemorrhagic telangiectasia.

Mnemonic
SMAD4 FGA
Methodology

Polymerase Chain Reaction/Sequencing/Multiplex Ligation-dependent Probe Amplification

Performed

Varies

Reported

28-35 days

New York DOH Approval Status
This test is New York DOH approved.
Specimen Required
Patient Preparation
Collect

Lavender (K2EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).

Specimen Preparation

Transport 3 mL whole blood. (Min: 2 mL)

Storage/Transport Temperature

Refrigerated.

Unacceptable Conditions
Remarks
Stability

Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months

Reference Interval
Interpretive Data

Background Information for Juvenile Polyposis (SMAD4) Sequencing and Deletion/Duplication:
Characteristics of Juvenile Polyposis Syndrome (JPS):
Gastrointestinal (GI) bleeding, multiple hamartomatous polyps in the GI tract, increased risk for GI carcinoma.
Characteristics of JP/Hereditary Hemorrhagic Telangiectasia (HHT):
Recurrent nosebleeds, telangiectases (mouth, face, hands, GI tract), arteriovenous malformations (lung, brain, liver, spine) and hamartomatous polyps in the GI tract.
Incidence:
1 in 16,000 to 1 in 100,000 for JPS; unknown for JP/HHT.
Inheritance:
Autosomal dominant; de novo mutations occur in 25 percent of JPS.
Penetrance:
Suspected to be greater than 90 percent for JPS.
Cause for JPS:
Mutations in SMAD4, BMPR1A and other unknown genes.
Cause for JP/HHT
: Mutations in SMAD4.
Clinical Sensitivity
: Approximately 25 percent for JPS; unknown for JP/HHT.
Methodology
: Bidirectional sequencing of the entire SMAD4 coding region and intron-exon boundaries. Multiplex ligation-dependent probe amplification (MLPA) to detect large SMAD4 coding region deletions/duplications.
Analytical Sensitivity and Specificity
: 99 percent.
Limitations:
Diagnostic errors can occur due to rare sequence variations. Breakpoints for large deletions/duplications will not be determined. This assay is not designed to detect somatic variants associated with malignancy. Interpretation of this test result may be impacted if the patient has had an allogeneic stem cell transplantation.

Compliance Statement C: For human genetic inheritable conditions and mutations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.

Counseling and informed consent are recommended for genetic testing. Consent forms are available online.

Note
Hotline History
N/A
CPT Codes

81405; 81406

Components
Component Test Code* Component Chart Name LOINC
2001973 JPS (SMAD4) Seq and Del/Dup Interp
2001975 SMAD4 FGA Specimen
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • SMAD4
  • SMAD4 sqeuending and deletion/duplication
Juvenile Polyposis (SMAD4) Sequencing and Deletion/Duplication